Ultrastructural Contributions to the Histogenesis of Pleomorphic Adenoma

Author(s):  
I. Dardick ◽  
A.W.P. van Nostrand ◽  
Diane Jeans ◽  
P. Rippstein ◽  
V. Edwards

Hospital, Ottawa, Canada and ^Hospital for Sick Children, Toronto, Canada. Survey-type electron micrographs correlated with semithin plastic sections (Fig. 2) were used in an ultrastructural study of 24 cases of salivary gland pleomorphic adenoma in order to assess tumor cell types and their organization in cellular regions and the gradual alterations occurring with the development of myxoid areas. Such micrographs confirm the presence of two principal cell types with smaller numbers of highly organized luminal epithelial cells forming duct- or acinar-like structures and more numerous, angular, mosaically or loosely arranged tumor cells surrounding luminal type cells. As is evident in Figure 1, darker staining, angular tumor cells just external to duct luminal cells have a specific and intimate association with luminal cells through cell processes and well developed desmosomes. Despite the lack of classical features of myoepithelial cells, the organizational arrangement of the two cell types and the distinctly different cytologic features of tumor cells external to luminal epithelial cells suggests that the former cell type represents myoepithelial cells modified as a result of neoplastic induction (Figs. 1 and 2).

2019 ◽  
Vol 22 (1) ◽  
pp. 122-126
Author(s):  
G. Farjanikish ◽  
A. Khodakaram-Tafti ◽  
M. Ghane

The lacrimal gland is a diamond-shaped, tubuloalveolar gland that secretes the serous component of tears. A four-year-old female crossbreed sheep suffering from left eye protrusion was referred to a Veterinary Hospital. Ophthalmic examination revealed epiphora, superficial ulcerative keratitis, corneal edema and neovascularisation. Moreover, ultrasound examination showed a large heterogeneous mass with variable reflectivity in the intraconal and extraconal spaces. Grossly, a 2.5×1.5×0.5 cm oval firm grayish mass was observed. Histopathologically, the mass was composed mainly by tubules with two cell types including cuboidal luminal epithelial cells and peripheral myoepithelial cells. The tubular structures were separated by proliferating myoepithelial cells. Mitotic figures, cellular pleomorphism and atypia were not seen. Immunohistochemically, most of the luminal epithelial cells showed an immunopositive reaction with a cytokeratin (AE1/AE3) marker. On the basis of these findings, the mass was diagnosed as a lacrimal gland adenoma.


Development ◽  
1986 ◽  
Vol 96 (1) ◽  
pp. 229-243
Author(s):  
E. Jane Ormerod ◽  
Philip S. Rudland

Rat mammary ducts, free of buds, can alone regenerate complete mammary trees when transplanted into the interscapular fat pads of syngeneic host rats. All the main mammary cell types are identified within such outgrowths. Epithelial cells, which show the presence of milk fat globule membrane antigens and microvilli on their luminal surfaces, line the ducts. Basal cells surrounding the ducts show characteristic features of myoepithelial cells: immunoreactive actin and keratin within the cytoplasm, myofilaments, pinocytotic vesicles and hemidesmosomal attachments to the basement membrane. Cells within the end buds and lateral buds, however, show few if any cytoplasmic myofilaments and are relatively undifferentiated in appearance. Intermediate morphologies between these cells and myoepithelial cells are seen nearer the ducts. In this respect they exactly resemble the cap cells found in terminal end buds (TEBs) of normal mammary glands. Occasional epithelial cells within alveolar buds show the presence of immunoreactive casein, which is a product of secretory alveolar cells in the normal rat mammary gland. Dissected terminal end buds can regenerate similar ductal outgrowths. Thus, ductal tissue alone can generate all the major mammary cell types seen in the normal gland, including the cap cells.


1986 ◽  
Vol 34 (7) ◽  
pp. 869-881 ◽  
Author(s):  
R B Nagle ◽  
W Böcker ◽  
J R Davis ◽  
H W Heid ◽  
M Kaufmann ◽  
...  

Two monoclonal antibodies, KA 1 and KA 4, raised against human epidermis, were biochemically and immunologically characterized and were shown to react with specific cytokeratin polypeptides. On frozen sections of human mammary gland, these antibodies distinguish between myoepithelial and luminal epithelial cells. We present evidence that in these cells KA 1 antibody recognized cytokeratin 5 and KA 4 antibody cytokeratin 19. In normal mammary tissue, KA 4 antibody invariably reacted with the epithelial cells lining the lumina of acini, ductules, ducts, and sinus. In contrast, KA 1 antibody decorated only the myoepithelial and basal epithelial cells of acini, ducts, and sinus. In ductules, however, KA 1 also stained the luminal cells. All 73 invasive lobular and ductal carcinomas studied reacted with KA 4 antibody; five of these were also positive, apparently in the same tumor cells, with KA 1. The tumor cells of in situ carcinomas were also stained in a homogeneous pattern with KA 4 antibody; KA 1 antibody reacted only with the surrounding myoepithelium. In epithelial hyperplasias, the proliferating cells were decorated by KA 1 and KA 4 antibodies in a heterogeneous pattern. Other antibodies were used for comparison. The results are discussed with respect to epithelial differentiation and pathogenesis and to the application of such antibodies for immunohistodiagnosis of mammary lesions.


1986 ◽  
Vol 34 (8) ◽  
pp. 1037-1046 ◽  
Author(s):  
A Sonnenberg ◽  
H Daams ◽  
M A Van der Valk ◽  
J Hilkens ◽  
J Hilgers

The development of the mouse mammary gland was studied immunohistochemically using monoclonal antibodies against cell surface and basement membrane proteins and a polyclonal antibody against keratin. We have identified three basic cell types: basal, myoepithelial, and epithelial cells. The epithelial cells can be subdivided into three immunologically related cell types: luminal type I, luminal type II, and alveolar cells. These five cell types appear at different stages of mammary gland development and have either acquired or lost one of the antibody-defined antigens. The cytoplasmic distribution of several of these antigens varied according to the location of the cells within the mammary gland. Epithelial cells which did not line the lumen expressed antigens throughout the cytoplasm. These antigens were demonstrated on the apical site in situations where the cells lined the lumen. One antigen became increasingly basolateral as the cells became attached to the basement membrane. The basal cells synthesize laminin and deposit it at the cell base. They are present in endbuds and ducts and are probably the stem cells of the mammary gland. Transitional forms have been demonstrated which developmentally link these cells with both myoepithelial and (luminal) epithelial cells.


Nature Aging ◽  
2021 ◽  
Vol 1 (9) ◽  
pp. 838-849 ◽  
Author(s):  
Sundus F. Shalabi ◽  
Masaru Miyano ◽  
Rosalyn W. Sayaman ◽  
Jennifer C. Lopez ◽  
Tiina A. Jokela ◽  
...  

AbstractDuring aging in the human mammary gland, luminal epithelial cells lose lineage fidelity by expressing markers normally expressed in myoepithelial cells. We hypothesize that loss of lineage fidelity is a general manifestation of epithelia that are susceptible to cancer initiation. In the present study, we show that histologically normal breast tissue from younger women who are susceptible to breast cancer, as a result of harboring a germline mutation in BRCA1, BRCA2 or PALB2 genes, exhibits hallmarks of accelerated aging. These include proportionately increased luminal epithelial cells that acquired myoepithelial markers, decreased proportions of myoepithelial cells and a basal differentiation bias or failure of differentiation of cKit+ progenitors. High-risk luminal and myoepithelial cells are transcriptionally enriched for genes of the opposite lineage, inflammatory- and cancer-related pathways. We have identified breast-aging hallmarks that reflect a convergent biology of cancer susceptibility, regardless of the specific underlying genetic or age-dependent risk or the associated breast cancer subtype.


2020 ◽  
Author(s):  
Fengfei Gu ◽  
Jiajin Wu ◽  
Senlin Zhu ◽  
Teresa G. Valencak ◽  
Jian-Xin Liu ◽  
...  

Abstract Background: Cow’s milk is a highly-nutritious dairy product that is widely consumed worldwide. It is secreted by the developed mammary gland (MG) of dairy cattle. However, a comprehensive understanding of cell-type diversity and cell function within bovine MG is lacking. In the current study, we used single-cell RNA sequencing to investigate the transcriptome of 24,472 high-quality MG cells isolated from newborn and adult cows. Results: Unbiased clustering analysis revealed the existence of 24 cell types, which could be divided into four categories: 9 immune, 3 epithelial, 9 fibroblast, and 3 endothelial cell types. Other cell subtypes were further identified based on re-clustering and pseudotemporal reconstruction of epithelial cells that included 3 mature luminal epithelial, 1 intermediate, and 2 progenitor cell subtypes. The individual top marker genes of these 3 mature luminal epithelial cell subtypes (L0, L1, and L5) were APOA1, STC2, and PTX3, which were further validated using immunofluorescence. Based on functional analysis, the L0, L1, and L5 cell subtypes were all involved in the upregulation of lipid metabolism, protein and hormone metabolism, and the immune response, respectively. Furthermore, we discovered a novel myofibroblast that expresses COL1A1 and CSN3, has visible epithelial-like characteristics, and shows the potential to differentiate into luminal epithelial cells, especially immune-sensing luminal cells (L5). Conclusions: We constructed the first single-cell atlas of the dairy cow MG, and our new findings of epithelial-like myofibroblast cells and their differentiation trajectories into luminal cells may provide novel insights into the development and lactogenesis in dairy cattle MGs.


Author(s):  
P. Sadhukhan ◽  
J. Chakraborty ◽  
M. S. Soloff ◽  
M. H. Wieder ◽  
D. Senitzer

The means to identify cells isolated from the mammary gland of the lactating rat as a prerequisite for cell purification have been developed.The cells were isolated from mammary tissue with 0. 1% collagenase, and they were visualized by scanning and transmission electron microscopy and by alkaline phosphatase cytochemistry.The milk-secreting cells have surface microvilli, whereas the surface of the myoepithelial cells is smooth (Fig. 1). The two isolated epithelial cell types are readily distinguishable by transmission electron microscopy (Fig. 2). The secretory cells contain vacuoles and a relatively extensive rough endoplasmic reticulum, whereas the myoepithelial cells contain a more osmiophilic cytoplasm, contractile filaments (Fig. 3) and elongate processes. These features are consistent with the appearance of the two cell types in situ.Incubation of isolated cells with oxytocin prior to glutaraldehyde fixation resulted in the contraction of the myoepithelial cell processes (Figs. 4 & 5). This physiological response to oxytocin shows that the isolated myoepithelial cells were intact. The appearance of isolated secretory cells was unchanged by the presence of oxytocin.


1985 ◽  
Vol 75 (1) ◽  
pp. 17-33
Author(s):  
J. Bartek ◽  
E.M. Durban ◽  
R.C. Hallowes ◽  
J. Taylor-Papadimitriou

Two monoclonal antibodies, BA16 and BA17, have been developed using a detergent-insoluble extract of human mammary epithelial organoids as immunogen. Indirect immunofluorescent staining of cultured cells showed that the component reacting with the antibodies was filamentous and the intensity of staining was stronger in mitotic cells. Immunoblotting of cell extracts showed that both antibodies react with only one band of 40 X 10(3) molecular weight, which was present in keratin-enriched extracts of cells or organoids. Furthermore, the tissue distribution of the component reacting with the antibodies was that predicted for human keratin 19. The antibodies showed differences in the intensity of staining of cells or tissue sections fixed and prepared in different ways indicating that they reacted with different epitopes. The pattern of expression of the 40 X 10(3) Mr keratin by normal mammary epithelial cells was investigated by immunoperoxidase staining of tissue sections, cultured milk cells, and organoids of different sizes cultured in collagen gels. It was found that basal or myoepithelial cells did not express this keratin. Some heterogeneity of expression of this component was seen in luminal epithelial cells, found almost exclusively in the smaller structures. These cells did, however, express other keratins characteristic of luminal cells. The distribution in the mammary tree of the luminal cells that did not express the 40 X 10(3) Mr keratin appears to be similar to that expected for cells with the proliferative potential to produce new terminal ductal lobular units or an increase in branching of existing terminal ductal lobular units. It is shown that these cells have considerable proliferative potential by the fact that they form large colonies in milk cell cultures.


2005 ◽  
Vol 72 (S1) ◽  
pp. 90-97 ◽  
Author(s):  
Eva Hellmén

Spontaneous mammary tumours are most frequently seen (apart from rodents) in women, female dogs and cats. The mammary gland is the most commonly affected organ for tumours in women and in female dogs. The mammary gland has a similar histology in the different species whereas the number of glands differs as well as the number of interlobular ducts that reach the nipple/teat. The parenchymatous tissue is composed of alveoli that turn into interlobular ducts. The whole ductal tree is outlined by a two-layered epithelium with the luminal epithelial cells adjacent to the lumen and the more sparse myoepithelial cells peripherally located to these. Different proteins such as growth factors regulate the mammary gland, as they do for all tissues in the body. In addition, sex hormones regulate the biology of the mammary gland. Oestrogen has the most pronounced effect on duct growth whereas progesterone promotes growth of the alveoli.


2002 ◽  
Vol 115 (1) ◽  
pp. 39-50 ◽  
Author(s):  
Thorarinn Gudjonsson ◽  
Lone Rønnov-Jessen ◽  
René Villadsen ◽  
Fritz Rank ◽  
Mina J. Bissell ◽  
...  

The signals that determine the correct polarity of breast epithelial structures in vivo are not understood. We have shown previously that luminal epithelial cells can be polarized when cultured within a reconstituted basement membrane gel. We reasoned that such cues in vivo may be given by myoepithelial cells. Accordingly, we used an assay where luminal epithelial cells are incorrectly polarized to test this hypothesis. We show that culturing human primary luminal epithelial cells within collagen-I gels leads to formation of structures with no lumina and with reverse polarity as judged by dual stainings for sialomucin, epithelial specific antigen or occludin. No basement membrane is deposited, and β4-integrin staining is negative. Addition of purified human myoepithelial cells isolated from normal glands corrects the inverse polarity, and leads to formation of double-layered acini with central lumina. Among the laminins present in the human breast basement membrane (laminin-1, -5 and -10/11), laminin-1 was unique in its ability to substitute for myoepithelial cells in polarity reversal.Myoepithelial cells were purified also from four different breast cancer sources including a biphasic cell line. Three out of four samples either totally lacked the ability to interact with luminal epithelial cells, or conveyed only correction of polarity in a fraction of acini. This behavior was directly related to the ability of the tumor myoepithelial cells to produce α-1 chain of laminin. In vivo, breast carcinomas were either negative for laminin-1 (7/12 biopsies) or showed a focal, fragmented deposition of a less intensely stained basement membrane (5/12 biopsies). Dual staining with myoepithelial markers revealed that tumor-associated myoepithelial cells were either negative or weakly positive for expression of laminin-1, establishing a strong correlation between loss of laminin-1 and breast cancer. We conclude that the double-layered breast acinus may be recapitulated in culture and that one reason for the ability of myoepithelial cells to induce polarity is because they are the only source of laminin-1 in the breast in vivo. A further conclusion is that a majority of tumor-derived/-associated myoepithelial cells are deficient in their ability to impart polarity because they have lost their ability to synthesize sufficient or functional laminin-1. These results have important implications for the role of myoepithelial cells in maintenance of polarity in normal breast and how they may function as structural tumor suppressors.


Sign in / Sign up

Export Citation Format

Share Document